The acquired immunodeficiency syndrome (AIDS) is a spectrum of diseases ranging from benign lymphoid hyperplasis to one or more opportunistic infections with T-lymphocyte dysfunction and the occurrence of otherwise rare neoplasms. One common feature of AIDS, at all stages of the syndrome, is the occurrence of human cytomegalovirus (HCMV) infection. In the general population, HCMV infection is commonly associated with transient immunodeficiency, and it is not known whether the presence of HCMV in AIDS signifies an etiologic cause of the syndrome or merely one more opportunistic infection. It is the aim of this proposal to determine HCMV is the primary inducing agent in AIDS. The proposal tests the hypothesis that HCMV induces AIDS in certain people by comparing AIDS patients with those having prodromal AIDS or having specific neoplasms of the lymphatic system, and with normal male homosexuals. The comparison will consist of a) isolation and characterization of wild isolates of HCMV using molecular and immunologic probes for single HCMV proteins or genes, b) determination of HCMV DNA and protein in tissue specimens from lymph node or tumor biopsies, and c) determination of the phenotype and function of immunoreactive populations of lymphoid cells generated in vitro during timulation with HCMV or with purified proteins of HCMV. In addition, an animal model of AIDS will be investigated using mice to determine if chronic exposure to purified proteins of HCMV can induce immunodeficiency. The proposal utilizes two recent developments in HCMV technology: the purification of single polypeptides of HCMV by high performance liquid chromatography and the synthesis and cloning of a single gene probe from the partial amino acid sequence of these polypeptides. A major 64-66 K dalton glycoprotein, which is common to HCMVs, forms the basis for these studies, and a DNA probe for this gene has been synthesized for this project. The proposal combines these molecular genetic methods with a pathologic analysis of lymphatic and neoplastic specimens uniquely available at City of Hope Medical Center and will determine whether markers of HCMV are more frequently found in tissues from AIDS.